Communication between and among cells, i.e., signal transduction and signaling, requires an ever more sophisticated armada of chemical and instrumental tools by researchers. This proposal tackles the demand for chemical initiation of substrate action in the communication process by developing new, fast acting [k(release) in nanosec.], efficient [phi = 0.1 -0.4] chromophores for phototriggers for substrate release of neurotransmitters (agonist and antagonists), enzyme substrates, inhibitors and prodrugs to be made available to the biology and medical communities to further our understanding of the mechanism and efficacy of substrate action. The spatial localization and temporal definition of biological responses afforded by photochemical release of substrates, whether in the development and mapping of neuronal networks, for drug delivery, or in mediating the visual process, are crucial to the understanding of the mechanism of action by substrates within and outside the cell, including the differing modes of action of released substrates in normal or diseased cells and tissues. Therefore, the principal objectives of this research program are the rational design, synthesis and photochemical study of a new generation of phototriggers or caged compounds. This proposal will specifically address the synthesis and development of new phototriggers (1) with solubility properties that range from lipophilic to hydrophilic, (2) that expand the spectral range from the UV into the visible region, (3) that are useful for caged neurotransmitters, nucleotides, and second messengers and pharmaceuticals by our collaborations in these fields, (4) that expand the repertoire of functional groups amenable to phototrigger release including the thiols, imidazoles, amines, phenols, hydroxyl, guanyl groups, (5) that are also chemically robust for applications in synthesis for combinatorial chemistry reagents, and (6) decage by 2-photon or multiphoton excitation.